Hypoxia induces upregulation of the deoxyribonuclease I gene in the human pancreatic cancer cell line QGP-1
- 作者：Yoshihiko Kominato ; Reiko Iida ; Tamiko Nakajima ; Yutaka Tajima ; Rie Takagi ; Chikako Makita ; Koichiro Kishi ; Misuzu Ueki ; Yasuyuki Kawai ; Toshihiro Yasuda
- 关键词：Deoxyribonuclease I ; Gene expression ; Promoter ; Sp1 ; Hypoxia ; QGP-1 cells
- 刊名：Biochimica et Biophysica Acta (BBA)/General Subjects
- 出版年：2007
- 期刊代码：16_03044165
- 类别：bio
- 出版时间：November 2007
- 卷：1770
- 期：11
- 页码：1567-1575
- 文件大小：593 K
摘要
We have previously demonstrated that ischemia caused by acute myocardial infarction induces an abrupt increase of serum deoxyribonuclease I (DNase I) activity. In this study, we examined whether hypoxia can affect the levels of DNase I activity and/or its transcripts in vitro. We first exposed the human pancreatic cancer cell line QGP-1, which is the first documented DNase-I-producing cell line, to hypoxia (2%O2), and found that this induced a significant increase in both the activity and transcripts of DNase I. This response was mediated by increased transcription only from exon 1a of the two alternative transcription-initiating exons utilized simultaneously in the human DNase I gene (DNASE1); exposure of QGP-1 cells to hypoxia for 24 h resulted in a 15-fold increase of DNASE1 transcripts starting from exon 1a compared with the expression level under normoxic conditions. Promoter, electrophoretic mobility shift, and chromatin immunoprecipitation assays with QGP-1 cells exposed to hypoxia or normoxia showed that the region just upstream from exon 1a was involved in this response in a hypoxia-induced factor-1-independent, but at least in a Sp1 transcription factor-dependent manner possibly through enhanced binding of Sp1 protein to the promoter. These results indicate that DNASE1 expression is upregulated by hypoxia in the cells.